What Is the D-Dimer Test?

The D-dimer test is a blood test that indicates whether blood clots are being actively formed somewhere within a person’s vascular system. This test can be helpful for diagnosing pulmonary embolus and deep vein thrombosis, as well as other medical conditions in which blood clots play a role.

However, there are limitations to the D-dimer test. In order to avoid being misled by it, doctors need to make sure they are using this test at the appropriate times, and must take due care in interpreting the results.

What Is D-Dimer?

The D-dimer test measures the amount of a protein called “fibrin D-dimer” in the blood. Fibrin D-dimer is produced whenever fibrin (a protein that is the chief component of a blood clot), is being actively degraded somewhere within the vascular system.

Blood clotting is an extremely complex process. It involves the activation of a series of circulating proteins (called the coagulation factors) that eventually produce long strands of fibrin. The “finished” blood clot is made up mainly of a tangle of fibrin strands, together with blood platelets that become trapped within the fibrin mass. 

A blood clot typically forms in order to prevent the leakage of blood (hemorrhage) from a damaged blood vessel. The clot plugs the leak.

However, whenever a blood clot forms it is important that its size is limited to prevent it from completely blocking the blood vessel it's trying to repair.

So, an intrinsic part of blood clot formation is a second process aimed at limiting its size. 

This second process, which limits the growth of a forming blood clot, is mediated by a protein called plasmin. Plasmin degrades the edges of the growing blood clot to make sure it stays just the right size.

Under normal conditions, therefore, a “healthy” blood clot represents a balance between these two opposite and simultaneous processes—the fibrin formation process and the plasmin-mediated fibrin degradation process.

Fibrin D-dimer is a degradation product of fibrin; it shows up in the blood whenever strands of fibrin are being broken up. Because fibrin formation and degradation both occur simultaneously during any blood clot, the amount of D-dimer found in the blood reflects the amount of active blood clot formation that is occurring in the body. 

In other words, an elevated blood level of D-dimer indicates that active blood clotting is taking place. 

Purpose of the Test

A D-dimer blood test can be useful in detecting whether or not an unusual degree of blood clotting is happening somewhere in the body. While this information can be potentially useful in evaluating a variety of medical conditions, the D-dimer test is most often helpful when either a pulmonary embolus or deep vein thrombosis are thought to be possible diagnoses.

A large variety of D-dimer blood tests have been developed and approved by the FDA over the past few decades. All of these are biochemical tests called immunoassays, which use a monoclonal antibody (an antibody that targets a specific substance) to detect certain portions of the D-dimer protein fragment in the blood.

Because these tests use various monoclonal antibodies and different methods of measuring how much of the monoclonal antibody has detected D-dimer fragments, the different kinds of D-dimer tests can give somewhat different results. So, it's important for each laboratory to establish its own ranges of normal and abnormal values.

Until the recent past, accurately measuring D-dimer levels required a central laboratory, which typically caused a delay of several hours before results could actually be reported. This delay made using highly accurate D-dimer testing in emergency departments (where they are often most useful) relatively impractical.

However, several rapid, point-of-care D-dimer blood tests have now been approved by the FDA, and most major hospitals have these tests readily available. As a result, D-dimer testing has become much more routine for evaluating people with a suspected pulmonary embolus or deep vein thrombosis.

Interpreting Results

Interpreting a D-dimer blood test requires a doctor to take at least two factors into consideration. First, is the level of D-dimer normal or elevated? And second, if the D-dimer level is elevated, is the reason for its elevation what you think it is?

Normal or Abnormal? 

Determining a strict cutoff between “normal” and “abnormal” D-dimer levels that works for each individual is not possible. Most of us have some amount of D-dimer circulating in our blood at any given time. This is because the events of daily life generally produce a certain amount of microtrauma to various blood vessels, which leads to blood clotting. 

The range of D-dimer levels associated with everyday living—that is, in people who do not have a pulmonary embolus, deep vein thrombosis, or any other pathology involving blood clotting—is relatively wide. So any threshold value that attempts to separate “normal” from “abnormal” D-dimer levels is going to be at least a little bit arbitrary. In order to estimate the most useful cutoff value between normal and abnormal D-dimer levels, laboratories have had to rely on population statistics.

Based on such statistics, most laboratories consider a D-dimer level of 500 nanograms per milliliter or higher to be "abnormal." But whatever the formal threshold might be for a particular laboratory, a doctor needs to take into account the lack of precision inherently involved in determining that threshold. So, for instance, a D-dimer level that's a little above the “normal” value may not actually indicate that the level is actually high for a specific individual. Similarly, a D-dimer level that's reported to be just below the cutoff value doesn't always mean that there is no abnormal blood clotting going on.

The bottom line is that the D-dimer test usually doesn't provide a definitive answer. It provides further evidence—evidence that must be considered in light of all the other clinical evidence available to a doctor—about the likelihood that a particular person is experiencing an abnormal level of blood clotting.

Why Is the D-Dimer High? 

When interpreting an elevated D-dimer test, the doctor also needs to consider the fact that a state of active blood clotting can be explained by many conditions aside from pulmonary embolus or deep vein thrombosis—including conditions of everyday life, as well as medical conditions. Things associated with high D-dimer levels include:

This long list of conditions associated with increased D-dimer levels often makes it difficult to be sure what, specifically, is causing a particular person to have an elevated D-dimer level. Many people suspected of having a pulmonary embolus or deep vein thrombosis will have one or more of the conditions on this list, in which case a high D-dimer level will have a limited diagnostic value.

When Is It Useful?

Despite these inherent limitations, there are several times when D-dimer testing is useful in clinical medicine. These include:

Pulmonary Embolus

The large majority of people with a recent pulmonary embolus will have an elevated D-dimer level. However, because so many other conditions also cause high D-dimer levels, this test alone can't be used to diagnose a pulmonary embolus.

Today, the D-dimer test is used to determine the need for further testing in conjunction with a formal estimate of a person’s risk of having had a pulmonary embolus. Doctors commonly use the Pulmonary Embolus Rule-Out Criteria (PERC) system as a method of estimating the risk of pulmonary embolus.

In people who are judged to be at low risk for pulmonary embolus, if the D-dimer test is not elevated, a pulmonary embolus can be essentially ruled out, and no further testing is needed. If the risk of having a pulmonary embolus is in the intermediate range, a low D-dimer test indicates that the odds are very low that a pulmonary embolus has occurred—and most doctors would not do additional testing. So, in these two groups of people being evaluated for a possible pulmonary embolus, a “normal” D-dimer test can be quite helpful. 

However, if the risk of a pulmonary embolus is judged to be high, a D-dimer test is not helpful either way, and there is no need to perform one. In such a person, whether the D-dimer test is normal or elevated, further testing is needed to make a definitive diagnosis.

Deep Vein Thrombosis

The D-dimer test is elevated in nearly every person with active deep vein thrombosis. For this reason, a low D-dimer test can be useful in ruling out a deep vein thrombosis, particularly in people whose clinical signs of actually having a deep vein thrombosis don't seem very convincing.

On the other hand, a high D-dimer test is not definitive in diagnosing deep vein thrombosis, since so many other conditions can cause high D-dimer levels. 

Other Medical Conditions

By far, the most common usage of the D-dimer test today is in evaluating people with suspected pulmonary embolus or deep vein thrombosis. However, the D-dimer test is potentially useful in a few other medical conditions as well. These include:

Coronary Artery Disease: High levels of D-dimer are associated with coronary artery disease. This is particularly true for people who have acute coronary syndrome (ACS)—the emergency conditions that result when an atherosclerotic plaque ruptures, leading to acute blood clot formation in a coronary artery. Accordingly, D-dimer levels have been reported to be elevated in people with myocardial infarctions and unstable angina. Furthermore, people treated for ACS who have persistently elevated D-dimer levels may have a higher probability of cardiac events recurring. While these associations between ACS and D-dimer levels are intriguing, more studies need to be done before guidelines can be developed to help doctors use D-dimer testing to manage people with coronary artery disease.

Disseminated Intravascular Coagulopathy (DIC): DIC is an uncommon, complex condition in which widespread blood clot formation occurs throughout the vascular system. DIC is caused by a variety of serious medical conditions, including cancer, widespread infections, liver disease, or severe tissue injury. DIC is difficult to treat and, if severe, is often fatal. However, there are various degrees of DIC and various scoring systems have been devised to categorize this condition, which can help to optimize treatment. Tests that measure fibrin degradation products, such as D-dimer, have been used as important components of some DIC scoring systems.

Hyperfibrinolysis: Hyperfibrinolysis is another type of blood clotting disorder, similar to DIC, and is associated with the same kinds of underlying medical conditions. The D-dimer test can sometimes be useful for evaluating this condition.

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